The objectives are (a) to enzymatically characterize peroxisomes from liver, kidney, and other tissues of the body, (b) to elucidate the different metabolic pathways in peroxisomes, (c) to relate these data to function of peroxisomes and metabolic diseases, (d) to monitor postnatal development of enzymes in peroxisomes of various tissues, and (e) to evaluate large increases in peroxisomal activity from the hypolipidemic drug, Clofibrate. This project is one of the major biochemical efforts to elucidate the properties of mammalian peroxisomes. It is a major effort because peroxisomes in different tissue vary in enzymatic composition, and their isolation is difficult. On this project liver peroxisomes were found to contain part of the cellular carnitine acyltransferases for fatty acid transport and NAD:glycerol phosphate dehydrogenase. Other enzymes involving aldehyde oxidase and fatty acid metabolism have been detected in liver peroxisomes and will be characterized. For investigations on peroxisomal glycerol phosphate dehydrogenase, it is proposed that some kinetically unfavorable dehydrogenase reactions occur in peroxisomes. NAD:glycerol phosphate dehydrogenase, at the branch point between carbohydrate and lipid metabolism, may be regulated by compartmentation between the cytoplasm and peroxisomes, by fatty acid inhibition, and by a peroxisomal flavopeptide chromophore which is necessary for dehydrogenase activity. Peroxisomal enzyme activity can be varied many fold. How factors effect these changes will be studied during development and after drug and hormone treatment. Projects will deal with postnatal peroxisomal development and peroxisomal proliferation during Clofibrate treatment. The hypothesis that liver peroxisomes are involved in lipid degradation will be tested by studying changes in peroxisomal enzymes during treatment by hypolipidemic drugs. Other proposed functions of peroxisomes and related metabolic diseases that could be examined are (a) weight and growth regulation by peroxisomal catabolism, (b) heat generation, particularly in the liver, and (c) such metabolic diseases as hyperoxaluria and glycinemia.